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Thermal Sensitive Liposomes Improve Delivery of Boronated Agents for Boron Neutron Capture Therapy

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Abstract

Purpose

Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation requires sufficient tumor boron delivery while minimizing nonspecific accumulation.

Methods

Thermal sensitive liposomes (TSLs) were designed to have a stable drug payload at physiological temperatures but engineered to have high permeability under mild hyperthermia.

Results

We found that TSLs improved the tumor-specific delivery of boronophenylalanine (BPA) and boronated 2-nitroimidazole derivative B-381 in D54 glioma cells. Uniquely, the 2-nitroimidazole moiety extended the tumor retention of boron content compared to BPA.

Conclusion

This is the first study to show the delivery of boronated compounds using TSLs for BNCT, and these results will provide the basis of future clinical trials using TSLs for BNCT.

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ACKNOWLEDGMENTS AND DISCLOSURES

The material in this manuscript is original, has not been previously published and has not been submitted for publication elsewhere while under consideration. Dr. Azab receives research support from Glycomimetics Inc., Arch Oncology and Cantex Pharmaceuticals; and is the founder and owner of Targeted Therapeutics LLC and Cellatrix LLC; however, these have no contribution to this study. Other authors state no conflicts of interest.

Funding

The study was supported by the National Cancer Institute of the National Institutes of Health (NIH) Award (U54CA199092). Kinan Alhallak was supported by the National Center for Advancing Translational Sciences (NCATS) of the NIH Award (TL1TR002344). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.

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Authors and Affiliations

  1. Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, 4511 Forest Park Ave., Room 3103, St. Louis, MO, 63108, USA

    Micah John Luderer, Barbara Muz, Kinan Alhallak, Jennifer Sun, Katherine Wasden, Nicole Guenthner, Pilar de la Puente, Cinzia Federico & Abdel Kareem Azab

  2. Department of Biomedical Engineering, Washington University, St. Louis, MO, USA

    Kinan Alhallak, Jennifer Sun & Abdel Kareem Azab

Authors
  1. Micah John Luderer
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  2. Barbara Muz
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  3. Kinan Alhallak
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  4. Jennifer Sun
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  5. Katherine Wasden
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  6. Nicole Guenthner
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  7. Pilar de la Puente
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  8. Cinzia Federico
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  9. Abdel Kareem Azab
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Correspondence to Abdel Kareem Azab.

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Luderer, M.J., Muz, B., Alhallak, K. et al. Thermal Sensitive Liposomes Improve Delivery of Boronated Agents for Boron Neutron Capture Therapy. Pharm Res 36, 144 (2019). https://doi.org/10.1007/s11095-019-2670-z

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  • DOI: https://doi.org/10.1007/s11095-019-2670-z

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